Desalted compositions of charged bio-organic substances are needed in many cases where a bio-organic substance is to be further processed. Traditional ion-exchange chromatography, fore instance, requires that the ionic strength of the solution from which a substance is to be adsorbed must have an ionic strength below a particular value that depends on the substance, other ions present, ion-exchanger to be used etc. Analytical methods used for bio-organic substances may be disturbed by the presence of salts leading to inaccurate results. Typical examples are mass spectrometry, elemental analyses, etc. Desalting is often an important process in the manufacturing of bio-organic substances of pharmaceutically acceptable purity and/or of purity acceptable for the food industry.
Conventional desalting procedures for bio-organic substances have been gel filtration, membrane filtration, ultrafiltration, dialysis etc. It has also been suggested to use (a) ion-exchangers in combination with a pH-switch for the desorption of the bio-organic substance in order to reduce the charge interaction the adsorbed substance and the ion-exchanger, and (b) strong ammonium ion-exchangers in combination with desorption with volatile buffers. See for instance Hirs et al., J. Biol. Chem 195 (1952) 669-683 and 219 (1956) 623-642; Hirs, Methods in Enzymology XI (ed. Hirs) (1967) 386-390; Dréze et al., and Analytica Chim Acta 11 (1954) 554-558, which are describing desalting of amino acids and short peptides. See also WO 9406822 (Upfront Chromatography) and WO 9965607 (Amersham Pharmacia Biotech AB) that suggest desalting of proteins.
U.S. Pat. No. 5,652,348 (Burton et al) suggests that by utilising chargeable ligands under hydrophobic interaction conditions desorption can be accomplished without salting or desalting. Hydrophobic interaction conditions mean that the ligand is in uncharged form and that the concentration of salt is high.